A number of antidepressants have emerged in the U.S. market in the past two decades. Selective serotonin reuptake inhibitors have become the drugs of choice in the treatment of depression, and they are also effective in the treatment of obsessive-compulsive disorder, panic disorder, and social phobia. New indications for selective serotonin reuptake inhibitors include post-traumatic stress disorder, premenstrual dysphoric disorder, and generalized anxiety disorder. Extended-release venlafaxine has recently been approved by the U.S. Food and Drug Administration for the treatment of generalized anxiety disorder. Mirtazapine, which is unrelated to the selective serotonin reuptake inhibitors, is unique in its action--stimulating the release of norepinephrine and serotonin. The choice of antidepressant drug depends on the agent's pharmacologic profile, secondary actions, and tolerability. Sexual dysfunction related to the use of antidepressants may be addressed by reducing the dosage, switching to another agent, or adding another drug to overcome the sexual side effects. Augmentation with lithium or triiodothyronine may be useful in patients who are partially or totally resistant to antidepressant treatment. Finally, tapering antidepressant medication may help to avoid discontinuation syndrome or antidepressant withdrawal.